tbuckley/cabot-search huggingface dataset:
Virtual Reality Exposure to a Healthy Weight Body Is a Promising Adjunct Treatment for Anorexia Nervosa
Authors: Simone C Behrens, Joachim Tesch, Philine J.B. Sun, Sebastian Starke, Michael J Black, Hannah Schneider, Jacopo Pruccoli, Stephan Zipfel, Katrin E. Giel
Journal: Psychotherapy and Psychosomatics (2023)

Treatment results of anorexia nervosa (AN) are modest, with fear of weight gain being a strong predictor of treatment outcome and relapse. Here, we present a virtual reality (VR) setup for exposure to healthy weight and evaluate its potential as an adjunct treatment for AN.In two studies, we investigate VR experience and clinical effects of VR exposure to higher weight in 20 women with high weight concern or shape concern and in 20 women with AN.In study 1, 90% of participants (18/20) reported symptoms of high arousal but verbalized low to medium levels of fear. Study 2 demonstrated that VR exposure to healthy weight induced high arousal in patients with AN and yielded a trend that four sessions of exposure improved fear of weight gain. Explorative analyses revealed three clusters of individual reactions to exposure, which need further exploration.VR exposure is a well-accepted and powerful tool for evoking fear of weight gain in patients with AN. We observed a statistical trend that repeated virtual exposure to healthy weight improved fear of weight gain with large effect sizes. Further studies are needed to determine the mechanisms and differential effects.
FDA Greenlights Automated Insulin Dosing System for Type 1 Diabetes
Authors: Emily Harris
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
“The Irish giant” and the questions haunting medical museums
Authors: Órla O’Donovan
Journal: BMJ (2023)

The remains of Charles Byrne, known as the "Irish giant," have become the subject of public discussion once more, reviving debates that continue to haunt medical and scientific museums.Instead of engaging in futile efforts to achieve closure on their colonial histories, museums must learn to live with the spectres of their past injustices that persist to the present.Decolonial scholars, such as Eve Tuck and C Ree, emphasise that being haunted by these injustices is the cost of the horrors and subjugations of colonisation and museums' role in this; it is "the relentless remembering and reminding that will not be appeased by settler society's assurances of innocence and reconciliation." 1 Museums must accept that they are haunted by their past by acknowledging and living with their colonial history, which they cannot resolve, forget, or hide.
Therapeutic targeting of metabolic vulnerabilities in cancers with MLL3/4-COMPASS epigenetic regulator mutations
Authors: Zibo Zhao, Kaixiang Cao, Jun Watanabe, Cassandra N. Philips, Jacob M. Zeidner, Yukitomo Ishi, Qixuan Wang, Sarah R. Gold, Katherine Junkins, Elizabeth T. Bartom, Feng Yue, Navdeep S. Chandel, Rintaro Hashizume, Issam Ben-Sahra, Ali Shilatifard
Journal: Journal of Clinical Investigation (2023)

Epigenetic status-altering mutations in chromatin-modifying enzymes are a feature of human diseases, including many cancers. However, the functional outcomes and cellular dependencies arising from these mutations remain unresolved. In this study, we investigated cellular dependencies, or vulnerabilities, that arise when enhancer function is compromised by loss of the frequently mutated COMPASS family members MLL3 and MLL4. CRISPR dropout screens in MLL3/4-depleted mouse embryonic stem cells (mESCs) revealed synthetic lethality upon suppression of purine and pyrimidine nucleotide synthesis pathways. Consistently, we observed a shift in metabolic activity toward increased purine synthesis in MLL3/4-KO mESCs. These cells also exhibited enhanced sensitivity to the purine synthesis inhibitor lometrexol, which induced a unique gene expression signature. RNA-Seq identified the top MLL3/4 target genes coinciding with suppression of purine metabolism, and tandem mass tag proteomic profiling further confirmed upregulation of purine synthesis in MLL3/4-KO cells. Mechanistically, we demonstrated that compensation by MLL1/COMPASS was underlying these effects. Finally, we demonstrated that tumors with MLL3 and/or MLL4 mutations were highly sensitive to lometrexol in vitro and in vivo, both in culture and in animal models of cancer. Our results depicted a targetable metabolic dependency arising from epigenetic factor deficiency, providing molecular insight to inform therapy for cancers with epigenetic alterations secondary to MLL3/4 COMPASS dysfunction.
Importance of Integrating Spiritual, Existential, Religious, and Theological Components in Psychedelic-Assisted Therapies
Authors: Roman Palitsky, Deanna M. Kaplan, Caroline Peacock, Ali John Zarrabi, Jessica L. Maples-Keller, George H. Grant, Boadie W. Dunlop, Charles L. Raison
Journal: JAMA Psychiatry (2023)

Importance Mounting evidence supports the role of spiritual, existential, religious, and theological components in mediating psychedelic-assisted therapy, yet integration of these elements into the clinical setting is lagging Observations Although psychedelic-assisted therapy commonly produces spiritually, existentially, religiously, or theologically relevant experiences for patients, these have not been systematically integrated into the psychotherapies that accompany therapeutic uses of psychedelics. As a key feature and potential mediator of therapeutic effects, evidence-based psychedelic-assisted therapies should include these topics in the treatment model. Research across multiple diagnostic targets and treatment contexts suggests that spiritually integrated psychotherapies are effective, feasible, and produce add-on benefits in spiritually, existentially, religiously, and theologically relevant outcomes, which are particularly germane to psychedelics. Established standards in spiritually integrated psychotherapy may be fruitfully applied to psychedelic-assisted therapy. Objectives for spiritually, existentially, religiously, and theologically integrated psychedelic-assisted therapy based on these standards and informed by considerations specific to psychedelics are recommended. Conclusions and Relevance Spiritual, existential, religious, and theological topics’ integration in psychedelic-assisted therapy is needed to ensure culturally competent, evidence-based treatment aligned with the highest standards of clinical care. Neglecting to address these topics can detract from cultural competence, contribute to risks for patients, and potentially undermine treatment success.
The Creation of DNA Origami‐Based Supramolecular Nanostructures for Cancer Therapy
Authors: Siyuan Zhang, Xin‐Yue Lou, Linlin Liu, Ying‐Wei Yang
Journal: Advanced Healthcare Materials (2023)

DNA origami technology, a unique type of DNA nanotechnology, has attracted much attention from researchers and is applied in various fields. Through exquisite design and precise self-assembly of four kinds of deoxyribonucleotides, DNA origami nanostructures are endowed with excellent programmability and addressability and show outstanding biocompatibility in bio-related applications, especially in cancer treatment. In this review, nanomaterials based on DNA origami for cancer therapy are concluded, whereby chemotherapy and photo-assisted therapy are the main focus. Furthermore, the working mechanisms of the functional materials attached to the rigid DNA structures to enable targeted delivery and circumvent drug resistance are also discussed. DNA origami nanostructures are valuable carriers for delivering multifunctional therapeutic agents and demonstrate great potential in cancer treatment both in vitro and in vivo. It is undoubted that DNA origami technology is a promising strategy for constructing versatile nanodevices in biological fields and will excel in human healthcare.
Correction: Mutations in α-synuclein, TDP-43 and tau prolong protein half-life through diminished degradation by lysosomal proteases
Authors: Paul J Sampognaro, Shruti Arya, Giselle M Knudsen, Emma L Gunderson, Angelica Sandoval-Perez, Molly Hodul, Kathryn Bowles, Charles S Craik, Matthew P Jacobson, Aimee W Kao
Journal: Molecular Neurodegeneration (2023)
Severity of All-Terrain Vehicle–Related Injuries by Age in Canada, 2002-2019
Authors: William MacDougall, Xuejing Jiang, Shamsia Sobhan, Robert Balshaw, Barbara Haas, Lynne Moore, Natalie Yanchar, Jonathan McGavock
Journal: JAMA Network Open (2023)

Importance Rates of pediatric hospitalizations following an injury while riding an all-terrain vehicle (ATV) are increasing. Few studies have compared the rates of severe injuries among children, adolescents, and adults. Objectives To investigate whether younger ATV riders are at risk for more severe ATV-related injuries. Design, Setting, and Participants This cross-sectional study was conducted using administrative data from hospitals in 9 provinces in Canada. Participants included patients admitted to hospitals with ATV-related injuries between 2002 and 2019. Statistical analysis was performed from June 2020 to September 2021. Exposures The primary exposure was age younger than 16 years. Comparison groups were youths aged 16 to 20 years and adults aged 21 years and older. Main Outcomes and Measures The main outcomes of interest were death, spinal cord injury, and an Injury Severity Score (ISS) greater than 25. Secondary outcomes were less severe injuries, including head injuries, crush type injuries, and fractures. Results Among 52 745 patients with complete data, 15% were youths younger than 16 years, 13% were youths aged 16 to 20 years, 82% were male, and 47% lived in rural areas. After adjusting for covariates, the odds of dying were higher among youths aged 16 to 20 years (adjusted odds ratio [aOR], 1.64; 95% CI, 1.04-2.60) compared with those younger than 16 years. Youths aged 16 to 20 years also had higher odds of spinal cord injury (aOR, 2.72; 95% CI, 1.80-4.20) and an injury severity score greater than 25 (aOR, 1.63; 95% CI, 1.36-1.96) compared with youths 16 years of age or less. Sex-specific analyses revealed these associations were greater for male youths aged 16 to 20 years (spinal cord injury: aOR, 3.81; 95% CI, 1.38-11.10, and dying in a hospital: aOR, 4.37; 95% CI, 1.19-21.02) than female youths aged 16 to 20 years. Conclusions and Relevance In this cross-sectional study of patients hospitalized for ATV injuries in Canada, youths aged 16 to 20 years and adults aged 21 years and older were at an increased risk of death and severe injuries compared with youths younger than 16 years. The increased risk of death and severe injuries was most evident among male patients.
NLRP3 inflammasome and interleukin-1 contributions to COVID-19-associated coagulopathy and immunothrombosis
Authors: Nicola Potere, Evan Garrad, Yogendra Kanthi, Marcello Di Nisio, Gilles Kaplanski, Aldo Bonaventura, Jean Marie Connors, Raffaele De Caterina, Antonio Abbate
Journal: Cardiovascular Research (2023)

Abstract Immunothrombosis—immune-mediated activation of coagulation—is protective against pathogens, but excessive immunothrombosis can result in pathological thrombosis and multiorgan damage, as in severe coronavirus disease 2019 (COVID-19). The NACHT-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome produces major proinflammatory cytokines of the interleukin (IL)-1 family, IL-1β and IL-18, and induces pyroptotic cell death. Activation of the NLRP3 inflammasome pathway also promotes immunothrombotic programs including release of neutrophil extracellular traps and tissue factor by leukocytes, and prothrombotic responses by platelets and the vascular endothelium. NLRP3 inflammasome activation occurs in patients with COVID-19 pneumonia. In preclinical models, NLRP3 inflammasome pathway blockade restrains COVID-19-like hyperinflammation and pathology. Anakinra, recombinant human IL-1 receptor antagonist, showed safety and efficacy and is approved for the treatment of hypoxaemic COVID-19 patients with early signs of hyperinflammation. The non-selective NLRP3 inhibitor colchicine reduced hospitalization and death in a subgroup of COVID-19 outpatients but is not approved for the treatment of COVID-19. Additional COVID-19 trials testing NLRP3 inflammasome pathway blockers are inconclusive or ongoing. We herein outline the contribution of immunothrombosis to COVID-19-associated coagulopathy, and review preclinical and clinical evidence suggesting an engagement of the NLRP3 inflammasome pathway in the immunothrombotic pathogenesis of COVID-19. We also summarize current efforts to target the NLRP3 inflammasome pathway in COVID-19, and discuss challenges, unmet gaps, and the therapeutic potential that inflammasome-targeted strategies may provide for inflammation-driven thrombotic disorders including COVID-19.
Missense Mutation in Human CHD4 Causes Ventricular Noncompaction by Repressing ADAMTS1
Authors: Wei Shi, Angel P. Scialdone, James I. Emerson, Liu Mei, Lauren K. Wasson, Haley A. Davies, Christine E. Seidman, Jonathan G. Seidman, Jeanette G. Cook, Frank L. Conlon
Journal: Circulation Research (2023)

Left ventricular noncompaction (LVNC) is a prevalent cardiomyopathy associated with excessive trabeculation and thin compact myocardium. Patients with LVNC are vulnerable to cardiac dysfunction and at high risk of sudden death. Although sporadic and inherited mutations in cardiac genes are implicated in LVNC, understanding of the mechanisms responsible for human LVNC is limited.
Treating the Side Effects of Exogenous Glucocorticoids; Can We Separate the <i>Good</i> From the <i>Bad</i>?
Authors: Riccardo Pofi, Giorgio Caratti, David W Ray, Jeremy W Tomlinson
Journal: Endocrine Reviews (2023)

Abstract It is estimated that 2% to 3% of the population are currently prescribed systemic or topical glucocorticoid treatment. The potent anti-inflammatory action of glucocorticoids to deliver therapeutic benefit is not in doubt. However, the side effects associated with their use, including central weight gain, hypertension, insulin resistance, type 2 diabetes (T2D), and osteoporosis, often collectively termed iatrogenic Cushing's syndrome, are associated with a significant health and economic burden. The precise cellular mechanisms underpinning the differential action of glucocorticoids to drive the desirable and undesirable effects are still not completely understood. Faced with the unmet clinical need to limit glucocorticoid-induced adverse effects alongside ensuring the preservation of anti-inflammatory actions, several strategies have been pursued. The coprescription of existing licensed drugs to treat incident adverse effects can be effective, but data examining the prevention of adverse effects are limited. Novel selective glucocorticoid receptor agonists and selective glucocorticoid receptor modulators have been designed that aim to specifically and selectively activate anti-inflammatory responses based upon their interaction with the glucocorticoid receptor. Several of these compounds are currently in clinical trials to evaluate their efficacy. More recently, strategies exploiting tissue-specific glucocorticoid metabolism through the isoforms of 11β-hydroxysteroid dehydrogenase has shown early potential, although data from clinical trials are limited. The aim of any treatment is to maximize benefit while minimizing risk, and within this review we define the adverse effect profile associated with glucocorticoid use and evaluate current and developing strategies that aim to limit side effects but preserve desirable therapeutic efficacy.
FH Variant Pathogenicity Promotes Purine Salvage Pathway Dependence in Kidney Cancer
Authors: Blake R. Wilde, Nishma Chakraborty, Nedas Matulionis, Stephanie Hernandez, Daiki Ueno, Michayla E. Gee, Edward D. Esplin, Karen Ouyang, Keith Nykamp, Brian Shuch, Heather R. Christofk
Journal: Cancer Discovery (2023)

Abstract Fumarate accumulation due to loss of fumarate hydratase (FH) drives cellular transformation. Germline FH alterations lead to hereditary leiomyomatosis and renal cell cancer (HLRCC) where patients are predisposed to an aggressive form of kidney cancer. There is an unmet need to classify FH variants by cancer-associated risk. We quantified catalytic efficiencies of 74 variants of uncertain significance. Over half were enzymatically inactive, which is strong evidence of pathogenicity. We next generated a panel of HLRCC cell lines expressing FH variants with a range of catalytic activities, then correlated fumarate levels with metabolic features. We found that fumarate accumulation blocks de novo purine biosynthesis, rendering FH-deficient cells reliant on purine salvage for proliferation. Genetic or pharmacologic inhibition of the purine salvage pathway reduced HLRCC tumor growth in vivo. These findings suggest the pathogenicity of patient-associated FH variants and reveal purine salvage as a targetable vulnerability in FH-deficient tumors. Significance: This study functionally characterizes patient-associated FH variants with unknown significance for pathogenicity. This study also reveals nucleotide salvage pathways as a targetable feature of FH-deficient cancers, which are shown to be sensitive to the purine salvage pathway inhibitor 6-mercaptopurine. This presents a new rapidly translatable treatment strategy for FH-deficient cancers. This article is featured in Selected Articles from This Issue, p. 1949
Machine Learning–Based Treatment Allocation for Recurrent Hepatocellular Carcinoma—Reply
Authors: Simone Famularo, Matteo Donadon, Guido Torzilli
Journal: JAMA Surgery (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Consensus report of the 2021 National Cancer Institute neuroendocrine tumor clinical trials planning meeting
Authors: Simron Singh, Thomas A Hope, Emily B Bergsland, Lisa Bodei, David L Bushnell, Jennifer A Chan, Beth R Chasen, Aman Chauhan, Satya Das, Arvind Dasari, Jaydira Del Rivero, Ghassan El-Haddad, Karyn A Goodman, Daniel M Halperin, Mark A Lewis, O Wolf Lindwasser, Sten Myrehaug, Nitya P Raj, Diane L Reidy-Lagunes, Heloisa P Soares, Jonathan R Strosberg, Elise C Kohn, Pamela L Kunz, Emily Bergsland, Tom Beveridge, Lisa Bodei, Anita Borek, Michelle Brockman, David Bushnell, Jacek Capala, Jennifer Chan, Beth Chasen, Aman Chauhan, Satya (Nanu) Das, N Arvind Dasari, Cynthia Davies-Venn, Jaydira Del Rivero, Sandra Demaria, Martha Donoghue, Jennifer Eads, Ghassan El-Haddad, Natalie Fielman, Lauren Fishbein, Germo Gericke, Karyn Goodman, Daniel Halperin, Andrew Hendifar, Rodney Hicks, Robert Hobbs, Timothy Hobday, Thomas Hope, Renuka Iyer, Deborah Jaffe, Andrew Kennedy, Elise Kohn, Matthew Kulke, Charles Kunos, Pamela L Kunz, Mark Lewis, Frank Lin, Wolf Lindwasser, Josh Mailman, Michael McDonald, Sandy McEwan, Sten Myrehaug, Antonio Nakasato, Steve Nothwehr, Fang-Shu Ou, Sukhmani Padda, Marianne Pavel, Anthony Pilowa, Nitya Raj, Brian Ramnaraign, Diane Reidy-Lagunes, Larry Rubinstein, Stephen Saletan, Manisha Shah, Simron Singh, Heloisa Soares, Michael Soulen, Jonathan Strosberg, Brian Untch, Mona Wahba, Rebecca Wong, James Yao
Journal: JNCI Journal of the National Cancer Institute (2023)

Important progress has been made over the last decade in the classification, imaging, and treatment of neuroendocrine neoplasm (NENs), with several new agents approved for use. Although the treatment options available for patients with well-differentiated neuroendocrine tumors (NETs) have greatly expanded, the rapidly changing landscape has presented several unanswered questions about how best to optimize, sequence, and individualize therapy. Perhaps the most important development over the last decade has been the approval of 177Lu-DOTATATE for treatment of gastroenteropancreatic-NETs, raising questions around optimal sequencing of peptide receptor radionuclide therapy (PRRT) relative to other therapeutic options, the role of re-treatment with PRRT, and whether PRRT can be further optimized through use of dosimetry among other approaches. The NET Task Force of the National Cancer Institute GI Steering Committee convened a clinical trial planning meeting in 2021 with multidisciplinary experts from academia, the federal government, industry, and patient advocates to develop NET clinical trials in the era of PRRT. Key clinical trial recommendations for development included 1) PRRT re-treatment, 2) PRRT and immunotherapy combinations, 3) PRRT and DNA damage repair inhibitor combinations, 4) treatment for liver-dominant disease, 5) treatment for PRRT-resistant disease, and 6) dosimetry-modified PRRT.